It has hitherto been known to prepare (+) biotin from amino acids viz. cystine, cysteine and serine. Prior art processes involving L-cystine as the precursor incorporate intramolecular radical cyclization (E. J. Corey, M. M. Mehrotra Tetrahedron Letters 29, 57 (1988) as the key step to construct the tetrahydrothiophene moiety of biotin. Another prior art process revolves around intramolecular cycloaddition (3+2) of derivatives of L-cystine (E. G. Baggiolini, H. L. Lee, G. Pizzolato and M. R. Uskokovic, J. Amer. Chem. Soc., 104, 6460-6462 (1982), and L-cysteine (H. L. Lee, E. G. Baggiolini and M. R. Uskokovic, Tetrahedron, 43, 4887 (1987). In another process starting from L-cysteine, a bicyclic hydantoin is the key intermediate leading to D(+) biotin. E. Poetsch and M. Casutt, EP 242,686 (1986); CA 108: 112077K (1988); Chimia 41, 148-150 (1987). In a totally different and novel approach, L-cysteine was converted to its thiazolidine derivative which on treatment with bromine is converted stereospecifically to a bicyclic intermediate as a single stereoisomer and eventually transformed to D(+) biotin (P. N. Confalone, E. G., Baggiolini, D. Lollar, and M. R. Uskokovic, J. Amer. Chem. Soc., 99, 7020-7026 (1977).
Hitherto known processes involve highly toxic and hazardous chemicals e.g. phosgene for the formation of hydantoin. Moreover the intramolecular radical cyclization leads to both six as well as the desired five membered ring system along with tin inclusion compounds as the undesired by-products.
In another prior art process involving intramolecular 3+2 cycloaddition reaction of nitrone, the precursor olefin is obtained as a mixture (9:1) of which the desired olefin has to be purified and separated by chromatography. Moreover, the chiral intermediates obtained during the above mentioned sequence of reactions were prone to racemization.
Another prior art process involving the intramolecular cyclization of thiazolidine required Collins oxidation as one of the steps. Use of heavy metals on an industrial scale would lead to problems during waste disposal. Moreover, Wittig reaction, on the aldehyde leads to a mixture of isomers which should be separated and the desired isomer subjected to further reactions leading to biotin.
The following abreviations are used in this application:
TBDMSOTf: tert-Butyldimethylsilyl trifluoromethanesulfonate PA0 TMSOTf: Trimethylsilyl trifluoromethanesulfonate PA0 LDA: Lithium diisopropylamide PA0 KOBut: Potassium tert-butoxide PA0 AgOTf: Silver trifluoromethanesulfonate PA0 TMSC1: Chlorotrimethylsilane PA0 TBDMSC1: tert-Butyldimethylsilyl chloride PA0 CSA: 10-Camphorsulfonic acid PA0 Et.sub.3 N: Triethylamine PA0 DIBAL: Diisobutylaluminium hydride PA0 PTSA: para-Toluenesulphonic acid